Ceramide-based risk score CERT-1 improves risk prediction for overall mortality and adverse cardiovascular outcomes in patients with and without cardiovascular disease: A prospective cohort study

Alessandro Mantovani; Gianluigi Lunardi; Stefano Bonapace; Agustin E Molinero; Riccardo Morandin; Veronica Fiorio; Giulio Molon; Christopher D Byrne; Giovanni Targher

doi:10.1111/dom.16156

Ceramide-based risk score CERT-1 improves risk prediction for overall mortality and adverse cardiovascular outcomes in patients with and without cardiovascular disease: A prospective cohort study

Diabetes Obes Metab. 2024 Dec 26. doi: 10.1111/dom.16156. Online ahead of print.

Authors

Affiliations

¹ Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
² Clinical Analysis Laboratory and Transfusional Medicine, Clinical Pharmacology, "IRCCS Sacro Cuore - Don Calabria" Hospital, Negrar di Valpolicella, Italy.
³ Division of Cardiology, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar di Valpolicella, Italy.
⁴ Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK.
⁵ Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK.
⁶ Department of Medicine, University of Verona, Verona, Italy.
⁷ Metabolic Diseases Research Unit, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar di Valpolicella, Italy.

PMID: 39726197
DOI: 10.1111/dom.16156

Abstract

Aims: Whether the plasma-based ceramide-based risk score CERT1 improves risk prediction for cardiovascular disease (CVD) is uncertain.

Materials and methods: Baseline and follow-up data were combined from two cohorts, 334 patients with established/suspected CVD and 196 patients with type 2 diabetes followed for a median of 74 months (interquartile range 54-79 months). For the calculation of CERT1 risk score, we measured four specific plasma ceramides [Cer(d18:1/16:0), Cer(d18:1/18:0) and Cer(d18:1/24:1)] and their ratios to Cer(d18:1/24:0). Based on the CERT1 risk score, patients were split into four risk categories (low, moderate, increased or high risk). The primary outcome was a composite of overall mortality and incident nonfatal CVD outcomes (including myocardial infarction, ischaemic stroke or permanent atrial fibrillation).

Results: One hundred and thirty-nine patients developed the primary composite outcome (72 nonfatal CVD outcomes and 67 total deaths) during follow-up. Baseline CERT1 risk categories were significantly associated with the risk of developing the primary composite outcome (adjusted HR for high vs. low-risk category 2.43, 95% CI 1.39-4.22, p = 0.002, and adjusted HR for increased vs. low-risk category 2.16, 95% CI 1.28-3.63, p = 0.004). Receiver operator characteristic curve analysis showed that adding CERT1 risk score to traditional CVD risk factors and pre-existing CVD, improved the discriminatory capability of the regression model for predicting the primary composite outcome (AUROC 0.691 [95% CI 0.674-0.769] vs. 0.722 [95% CI 0.642-0.742], p = 0.0275).

Conclusions: The ceramide-based risk score CERT1 risk score improves risk prediction for long-term risk of overall mortality and adverse cardiovascular outcomes in patients with and without CVD.

Keywords: CERT1 score; CVD; cardiovascular morbidity; mortality; plasma ceramides.